Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease.
Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease.
复制标题
酒精性肝病中Bmal1通过糖酵解途径调控巨噬细胞极化
DOI：
10.3389/fphar.2021.640521
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Zhou Y;Wu M;Xu L;Cheng J;Shen J;Yang T;Zhang L
肝巨噬细胞在酒精喂养引起的炎症中起关键作用。在此过程中，巨噬细胞表型的变化以多种方式引发炎症反应。此外，越来越多的证据表明，脑和肌肉类alt - like蛋白1 （Bmal1）被认为是巨噬细胞转化的关键调节因子。在我们的研究中，Bmal1在etoh喂养的小鼠组织样本和乙醇诱导的RAW264.7细胞中检测到低表达。肝脏特异性过表达Bmal1后，巨噬细胞M1标记物明显下调，M2标记物则相反，呈上升趋势。此外，过量表达Bmal1的酒精喂养小鼠的酒精性肝脏病变也得到改善。在此基础上，我们还发现糖酵解途径可以调节巨噬细胞的极化。体外阻断糖酵解途径可显著抑制m1型极化。重要的是，Bmal1过表达后糖酵解水平也受到抑制。Bmal1通过与S100A9蛋白相互作用，对糖酵解产生负调控作用。进一步研究表明，Bmal1对酒精性肝病（ALD）的缓解与糖酵解途径抑制和M1巨噬细胞极化有关。总之，我们证明了Bmal1是一个能够缓解ALD的基因，这种作用可能为改变巨噬细胞表型以调节ALD中的炎症反应提供新的见解。
Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. In vitro, blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What’s more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD.
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DOI：
10.1126/science.1243417
发表时间：
2013-11-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Bass J
影响因子：
4.6
作者：
Oishi Y;Hayashi S;Isagawa T;Oshima M;Iwama A;Shimba S;Okamura H;Manabe I
通讯作者：
Manabe I
影响因子：
5.6
作者：
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通讯作者：
Papa A
影响因子：
5.5
作者：
Rousseau, Louis-Simon;Pare, Guillaume;Fernandes, Maria
通讯作者：
Fernandes, Maria
DOI：
10.1073/pnas.1800431115
发表时间：
2018-09-04
影响因子：
11.1
作者：
Early JO;Menon D;Wyse CA;Cervantes-Silva MP;Zaslona Z;Carroll RG;Palsson-McDermott EM;Angiari S;Ryan DG;Corcoran SE;Timmons G;Geiger SS;Fitzpatrick DJ;O'Connell D;Xavier RJ;Hokamp K;O'Neill LAJ;Curtis AM
通讯作者：
Curtis AM